In collaboration with Dr. Patrick Browns lab, we conducted a preliminary study that demonstrated the utility of the cDNA microarray technique to identify genes that are differentially expressed in skeletal muscle biopsies of insulin resistant and insulin sensitive subjects. Currently, we are performing a similar comparison using more subjects and a more comprehensive method, oligonucleotide array. Previous studies have indicated strong correlations between biochemical characteristics of primary cultured skeletal muscle cells and clinical parameters of the donors. To determine which of the differentially expressed genes in muscle tissue of insulin resistant vs. insulin sensitive subjects may be primary, rather than secondary abnormalities, we propose also to compare the gene profiles of the cognate cultured myoblasts and myotubes. Similar comparisons will be made to identify obesity susceptibility genes using freshly isolated adipocytes and cultured pre-adipocytes from lean and obese Pima Indians. - insulin resistant, insulin sensitive, microarray technology - Human Subjects"